INDUCTION OF RAT-LIVER MICROSOMAL EPOXIDE HYDROLASE BY ITS ENDOGENOUSSUBSTRATE 16-ALPHA, 17-ALPHA-EPOXYESTRA-1,3,5-TRIEN-3-OL

1. The influence of the endogenous steroid epoxides 16 alpha, 17 alpha -epoxyestra-1,3,5(10)-trien-3-ol (estroxide) and 16 alpha, 17 alpha-ex poxiandrost-4-en-3-one (androstene oxide) and their metabolic precurso rs estra-1,3,5(10), 16-tetraen-3-ol (estratetraenol) and androsta-4, 1 6-dien-3-one (androstadienone) on the specific activities of hepatic m icrosomal and soluble epoxide hydrolase, glutathione S-transferase, di hydrodiol dehydrogenase, and 7-ethoxycoumarin deethylase was investiga ted in the male Sprague-Dawley rat. 2. Both estroxide and estratetraen ol induced microsomal epoxide hydrolase activity towards styrene oxide and estroxide itself 2-2.5-fold and glutathione conjugation of 1-chlo ro-2,4-dinitrobenzene (CDNB) 1.6-fold after intraperitoneal administra tion of a high dose of compound (300 mg per kg of body weight). 3. In addition, estroxide decreased 7-ethoxycoumarin deethylation down to 20 % of the activity observed in the untreated rat, whereas estratetraeno l enhanced the activity of soluble epoxide hydrolase towards trans-sti lbene oxide by a factor of 1.7. 4. In contrast, neither androstene oxi de nor androstadienone showed a significant influence on any of the pa rameters under investigation. Dihydrodiol dehydrogenase was not signif icantly changed by any of the treatments.